Diffusion Weighted Imaging in Pediatric Body: Update

Transcription

1 Diffusion Weighted Imaging in Pediatric Body: Update Govind Chavhan, MD DABR Diagnostic Imaging Department The Hospital for Sick Children and University of Toronto, Canada 2 Outline Principles of diffusion weighted imaging (DWI) Technique of diffusion weighted imaging (DWI) in pediatric body MRI Normal signal intensities of various body tissues on DWI in children. Emerging applications of diffusion in pediatric body imaging. 1

2 3 Principles Diffusion = random motion of water molecules The variation in mobility of water molecules between different tissues results in different signal intensity on diffusion imaging Isotropic diffusion = chance that molecule will move in any direction is equal Routine DWI Anisotropic diffusion = molecules move in a preferential direction e.g. along fiber tracts DTI 5. What does diffusion tell us? Increased diffusion Decreased diffusion DWI The signal intensity on DWI indirectly informs us about the microenvironment within the tissue. 2

3 6 Technique 7 Technique: diffusion weighting and b-value Stejskal-Tanner sequence b-value = degree of diffusion weighting b-value (sec/mm 2 ) depends on and increases with the amplitude, duration of application and separation of diffusion gradients (DG). 3

4 8 Technique: diffusion weighting and b-value As b-value increases sensitivity of the sequence to the diffusion increases and signal from the water molecules reduces. B = 0 9 Technique: diffusion weighting and b-value As b-value increases sensitivity of the sequence to the diffusion increases and signal from the water molecules reduces. B = 100 4

5 10 Technique: diffusion weighting and b-value As b-value increases sensitivity of the sequence to the diffusion increases and signal from the water molecules reduces. B = Technique: diffusion weighting and b-value At high b-value, tissues with reduced water molecule mobility, long T2 relaxation time or both will have high signal. B = 600 5

6 12 Technique: choice of b-values Minimum 2 b-values required for calculation Depends on The organ of the interest T2 value of the organ e.g. T2 of liver is approx 46 ms as compared to 90 ms for gray matter. The purpose- lesion detection versus characterization To certain extent- field strength Choose- Low b-values (50-100)- for lesion detection High b-values ( )- for lesion characterization Very high b-values ( )- for DWIBS Typical b-values in children (sec/mm 2 ) Liver: 0, 100, 600 Renal: 0, 100, 800 Bowel: 0, 400, 800 MSK: 0, 400, Technique: sequences 1. Single-shot fast spin-echo echo-planar sequence Most frequently used sequence 4 Can be acquired with - Breath-hold - Respiratory triggering - Free breathing 2. DWIBS (Diffusion weighted imaging with background body signal suppression) 7,8 Free breathing Heavy diffusion weighting (b-values sec/mm 2) Fat suppression by inversion pulse or CHESS Only structures with restricted diffusion seen on final images Used for Whole-body DWI Brachial plexus 6

7 14 Assessment 15 DWI: Qualitative assessment Typical diffusion images available for review: b-value 0, highest b-value (diffusion-weighted image) and map T2 B600 e d SPEN DWI bright, dark = diffusion restriction (eg. Spleen, spinal cord) DWI dark, bright = increased diffusion (eg. CSF in spinal canal) DWI bright, bright = T2 shine through (eg. Gallbladder) DWI dark, dark = proton poor tissue/susceptibility (eg. Bone cortex) 7

8 16 DWI: Quantitative assessment- maps are derived from multiple b-value images. L K S measurements: Approximate in the region of interest (ROI) in: Liver (L): 1.41x 10-3 mm 2 /sec Kidney (K): 2.2 x 10-3 mm 2 /sec Spleen (S): 0.97 x 10-3 mm 2 /sec 17 DWI: Quantitative assessment- IVIM IntraVoxel Incoherent Motion Mono-exponential vs Bi-exponential 8

9 18 DWI: Quantitative assessment- IVIM Fast vs slow diffusion D* = pseudodiffusion- capillary perfusion D = pure diffusion- tissue diffusion f = perfusion fraction 19 DWI: Quantitative assessment- DKI SEM Diffusion kurtosis- DKI Non-Gaussian diffusion behavior Ultra-high b-values > D app and K app Intracellular compartment Image from: Rosenkrantz AB, et al. JMRI 2015; 42: Stretched-exponential model Subvoxel heterogeneity α and DDC Ultra-high b-values upto Image from: Bennett KM, et al. MRM 2003; 50:

10 20 What determines signal intensity on DWI? 1. Mobility of water molecules = 2. T2 relaxation time. Abdominal structures Normal T2 relaxation time and at 1.5 T T2 relaxation time (ms) 10 (x 10-3 mm 2 /sec) 11 (Adults) (x 10-3 mm 2 /sec) * (Children) Spleen Liver Pancreas Kidney Gallbladder Back muscles Endometrium , (x 10-3 mm 2 (Children) * Gawande RS, et al. Pediatr Radiol 2013; Neubauer H, et al. Pediatr Radiol 2013; 43: What is normal?: Spleen and spinal cord b600 Any lymphoid tissue including normal lymph nodes, spleen and thymus are normally diffusion restricted. The spinal cord is normally restricted and may be used as a reference to judge diffusion restriction in other structures. Ovary, testis, adrenal glands, neonatal kidneys and red marrow are normally restricted. * Chavhan GB, et al. Pediatr Radiol 2016; first MRC suppl 10

11 22 What is normal? * Chavhan GB, et al. Pediatr Radiol 2016; first MRC supplement 30 Clinical applications 11

12 32 Liver Imaging: Lesion detection DWI can be used in three ways in liver imaging: 1. Lesion detection, 2. Lesion characterization and 3. Hepatic fibrosis and cirrhosis evaluation. Lesion detection: Low b-value images (50-100) make vessels dark making easier to detect T2 hyperintense hepatic lesions Metastases detection T2-W B Liver Imaging: Lesion characterization In adult studies 4, 24-27, malignant hepatic lesions like HCC and mets show low ; benign lesions like hemangioma and cysts show high ; cellular benign lesions like adenoma and FNH show intermediate. Ax T2 Portal venous b600 Path: Hepatoblastoma (Epithelial- fetal+embryonal) 12

13 34 Liver Imaging: Lesion characterization 89 children: 38 boys; 51 girls with a mean age of 10 years (3 months-18 years) Total 112 focal hepatic: 92 benign and 20 malignant Final diagnosis: Pathology in 43 lesions; clinical and imaging features and follow up (mean period 21 months) in 69 lesions Caro-Dominguez P, Gupta A, Chavhan G. Pediatric Radiology In press 35 Liver Imaging: Lesion characterization Qualitative DWI assessment All malignant lesions showed qualitative diffusion restriction Except abscesses none of the benign lesions showed diffusion restriction Excluding abscesses, there was significant association between diffusion restriction with malignancy and nonrestriction with benignancy (Fisher s exact test p<0.0001). Caro-Dominguez P, Gupta A, Chavhan G. Pediatric Radiology In press 13

14 36 Liver Imaging: Lesion characterization Quantitative DWI assessment Mean normalized values of malignant lesions [1.23, SD 0.24 (x 10-3 mm 2 /sec)] was lower than benign lesions excluding abscesses [1.62, SD 0.67 (x 10-3 mm 2 /sec)]. This difference was significant using student s t-test (p<0.015) Caro-Dominguez P, Gupta A, Chavhan G. Pediatric Radiology In press 37 Liver Imaging: Lesion characterization Quantitative DWI assessment An value cut-off of 1.2 x 10-3 mm 2 /sec yielded a sensitivity of 78% and a specificity of 54% for differentiation of benign from malignant lesion. 14

15 38 Liver Imaging: Lesion characterization Quantitative DWI assessment Significant overlap of normalized between benign and malignant lesions with wide range for each diagnosis 39 Liver Imaging: Lesion characterization Restricted liver lesion Biopsy Quantitative ( measurements) not yet robust in differentiation. The differentiation of malignant from benign lesions is hampered by less reproducibility, variability of measurements up to 30% 6 ; and significant overlap of of benign and malignant lesions 4. Caro-Dominguez P, Gupta A, Chavhan G. Pediatric Radiology In press 15

16 40 Liver Imaging: Lesion characterization T2 Art PV 45 min Focal Nodular Hyperplasia B Liver Imaging: Lesion characterization Art PV Equilibrium 5 min T2 Hemangioma B600 16

17 42 Spleen as a reference Liver lesion looking like spleen on all sequences is bad! Ax T2 Ax T1 b800 Arterial Fibrolamellar HCC Equilibrium 43 Liver Imaging: Fibrosis and cirrhosis is reduced in hepatic fibrosis. Thought to be related to accumulation of proton-poor connective tissue and reduced capillary perfusion 4. Can be used for detection and quantification of fibrosis and cirrhosis 3,4. Few pediatric studies showing utility of measurement to predict liver fibrosis, following up severity of cirrhosis* and in Liver Liver Liver Cirrhosis Spl Spl PV B600 Spl * Peng SS, et al. Eur Radiol 2015; Wolff D, et al. Int J Cardiol 2016 Jan; 202:

18 44 Body Tumors: Detection and characterization DWI can be used in four ways in body tumor imaging: 1. Tumor detection and characterization, 2. Biopsy guidance 3. Monitoring treatment response and 4. Whole-body DWI. 45 Body Tumors: Detection and characterization Restricted tumors are usually brightest among all structures making them easier to detect on DWI. T2 T1 Gd+ B600 Recurrent renal sarcoma 18

19 46 Body Tumors: Detection and characterization Malignant peritoneal thickening and tiny nodular deposits easily detected by DWI. T2 B600 T1 Gd+ Peritoneal deposit from ovarian yolk sac tumor recurrence 47 Body Tumors: Detection and characterization Adult studies indicate that malignant body tumors tend to be diffusion restricted. A few pediatric studies reflect the adult findings 34,58. T1 Gd+ B600 B600 Wilms tumor with hepatic mets STIR 19

20 48 Body Tumors: Detection and characterization In pediatric studies, neuroblastoma is found to be restricted and has less than ganglioneuroma that may help to differentiate them 32,33. T2 Neuroblastoma B600 T2 B800 Ganglioneuroma 49 Body Tumors: Detection and characterization Sarcomas are restricted. Rhabdomyosarcoma T2 B600 T1 T1 Gd+ 20

21 50 Body Tumors: Detection and characterization Does restriction in pediatric body tumor means malignant tumor? Mostly Yes! (we still have to learn a lot) 51 Body Tumors: Detection and characterization Benign neurogenic tumors like schwannoma. Benign germ cell tumors especially ovarian T1 T2 T1 Gd+ B600 Mature germ cell tumor of ovary 21

22 52 Body Tumors: Biopsy guidance Can be used in combination with other sequences for biopsy guidance Cor STIR T1 T2 B600 e 53 Body Tumors: Biopsy guidance 2 months later Undifferentiated Sarcoma 22

23 54 Body Tumors: Therapy response increases with therapy. Therapy In a small pediatric study, hepatoblastoma and Wilms tumor showed increase in with chemotherapy but 2 RMS did not show increase in the despite positive response to chemotherapy on histopathology*. Recently, whole tumor predicted response in Wilms Hampered by less reproducibility, variability of measurements and lack of standardization of technique. * McDonald K, et al. Pediatr Radiol 2011; Littooij A, et al. Pediatr Radiol 2015; 45: T2 Body Tumors: Therapy response B600 Neuroblastoma Stage IV Pelvic 14yrs Baseline = Cycles = 0.68 MIBG therapy = MIBG therapy + new chemo =

24 56 Whole-body DWI, especially DWIBS, has potential to detect mets in solid organs. Combination of WB MRI with WB- DWI has potential to replace or complement PET for lymphoma evaluation Promising results in lymphoma staging But few limitations- Lungs Lymph nodes Red marrow Tumors: Whole-body DWI * Littooij AS et al. Eur Radiol 2014; Littooij A, et al. JMRI 2015; 42: Bowel Imaging: Detection of inflammation DWI can be used in 3 ways in inflammatory bowel disease: 1. detection of inflammation 42-48, 2. detection of associated lymph nodes 3. detection of abscess and fistulas. T2 Ax VIBE post Gad Crohn disease DWI b = 800 DWI 24

25 60 Bowel Imaging: Roles of DWI DWI helps to detect Good correlation between signs of active inflammation on conventional MRE and diffusion restriction* DWI alone not as good as post-gd imaging for detection of active inflammation but addition of DWI increases accuracy # DWI more sensitive for detection of active inflammation than post-gd imaging Neubauer H, et al. Pediatr Radiol 2013; 43: *Ream JM, et al. Pediatr Radiol 2013; 43: #Shenoy-Bhangle AS, et al. Pediatr Radiol 2016; 46:34-42 $Dubron C, et al. Br J Radiol 2016; 89(1060): Bowel Imaging: Roles of DWI Qualitative and quantitative DWI not as good as conventional MRE to detect clinically active inflammation (wpcdai and PUCAI) AUC AUC IBD vs No IBD Active IBD vs No activity AlSabban Z et al. Clinical Imaging 2017; 41:

26 62 Bowel Imaging: pitfalls Terminal ileum can normally be slightly bright on DWI! Artifacts from fecal loading B800 B800 T2 Normal TI slightly bright No IBD T1 Gd+ Artifactual rectal wall hyperintensity from feces 60 Bowel Imaging: Roles of DWI Overall, DWI adds little over conventional MRE due to poor specificity and pitfalls May have value when Gad cannot be injected 26

27 63 Other applications Pelvic inflammatory disease in teenage girls. To find gonads in disorder of sex development (DSD) with ambiguous genitalia. To find ovaries in cases with pelvic mass and abdominal testes in undescended testes 51. T1 Gd+ B800 T1 Gd+ B800 Tubo-ovarian abscess (arrows) with right inguinal lymph node abscess (arrowheads) 64 Summary DWI good complementary sequence for detection Helps in characterization of lesions like tumor and abscess Not yet robust for staging and therapy response assessment 27

28 65 Summary Mikewires.com Quantitative DWI holds great promise as biomarker but needs standardization of technique! Interesting to see what other models like IVIM play. Thank you 28